Liquid-liquid immiscibility in model membranes activates secretory phospholipase A2
Kerstin Wagner1, Bernard Desbat, Gerald Brezesinski
1Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany. wagner@mpikg.mpg.de
Biochimica Et Biophysica Acta
|October 30, 2007
Summary
Liquid-liquid immiscibility in model membranes activates secretory phospholipase A2 (sPLA2). This membrane domain coexistence, crucial for sPLA2 activity, is relevant to biological membrane rafts.
Area of Science:
- Biochemistry
- Membrane Biophysics
- Enzymology
Background:
- Secretory phospholipase A2 (sPLA2) hydrolyzes phosphatidylcholines (PC) into signaling molecules.
- sPLA2 activity is modulated by membrane structure, including defects, curvature, and micro-heterogeneity.
- The role of liquid-liquid immiscibility in sPLA2 activation remains to be fully elucidated.
Purpose of the Study:
- To investigate if liquid-liquid immiscibility in model membranes is sufficient to activate sPLA2.
- To determine the critical surface pressure for sPLA2 activation in dimyristoyl-PC/cholesterol monolayers.
- To correlate sPLA2 activation with the phase behavior of lipid mixtures.
Main Methods:
- Utilized infrared reflection-absorption spectroscopy (IRRAS) and polarization-modulated (PM-IRRAS).
- Studied the hydrolytic activity of cobra-venom sPLA2 on mixed monolayers of dimyristoyl-PC (DMPC) and cholesterol.
- Measured the lag phase of sPLA2 activity at varying surface pressures.
Main Results:
- sPLA2 activation was observed below a critical surface pressure of 12 mN/m, with no lag phase.
- The lag phase of sPLA2 activity increased exponentially with surface pressures above 12 mN/m, indicating hampered activation.
- The critical surface pressure for sPLA2 activation correlated with the critical miscibility pressure of the DMPC/cholesterol system.
Conclusions:
- Coexisting liquid-phase domains, indicative of liquid-liquid immiscibility, are sufficient to activate sPLA2.
- Liquid-liquid immiscibility represents a novel activating mechanism for sPLA2.
- This finding is relevant to biological membranes, particularly membrane rafts, which exhibit similar domain structures.
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